The Population Confirmation About The Positive Results Of Genome-Wide Association Study In Schizophrenia

BackgroundGenetics plays very important role in the mechanism of schizophrenia.So far,we haven’t found any one gene to explain schizophrenia completely. Schizophrenia (Sch) is a mental disorder which is with high heterogeneity. Much of these risk gene maybe related with amounts of single nucleotide polymorphism on these genes. By means of linkage disequilibrium analysis and association study of candidate genes,we find that there maybe some genes related to schizophrenia ,such as the regions 6p24-22、13ql4-q33、 8p22-p21 of genes.But the effect size is small(OR<1.5).And every result from different professors are usually different and even we cannot replicate the course of the experiments.Before we recognize the truth of schizophrenia,we need to find the functionable snps, susceptible snps and the cooperation effect within the genes which are meaningful for the biology of schizophrenia.ObjectionsBy means of group of verification which are gotten by large samples, we found many impressionable targets which have substantial correlation with the mechanism of schizophrenia, exploring whether there is a common effect in these multiple minor genes which is the susceptibility locus and providing referential theoretical basis for revealing the mechanism of molecular genetics of schizophrenia.MethodsAt first, based on the positive results of GWAS of past experiment of 300 schizophrenia patients,we used R-language to screen 500 related SNPs(p<5×10-8),and then searched the information of these genes which were related to schizophrenia on NCBI and Hapmap.We calculated the FPR and OR between 0.9-1.1.The first 20 SNPs were screened out.We chose 202 GWAS genes from the catalog and analyzed the pathway with WEB pathway.And then we analyzed with K-clique to measure the cooperation of schizophrenia and metabolism.In order to verify the candidate SNPs, we cooperated the Catalog and dbgap to share the data base using methods of Gene ontology.We used the methods of GSEA to screen the same background of function among the 202 genes to be verified. By means of Pathway,we can recognize the positive genes which were associated with schizophrenia. At last, we’ll focus the information of genes and SNPs in NCBI and Hapmap.We use the prior GWAS data of 300 cases of samples to do the bioinformatics Pathway analysis with selecting ,susceptible genes which are related to Schizophrenia. Based on the prior GWAS data we choose 20 SNPs on the genes which are strongly associated with schizophrenia and genotype the snps which influence the gene expression.We choose our Chinese han nationality who are schizophrenia patients 1000 cases as patients’ group and then also choose the healthy Chinese han normal people 1000 cases as our control group and then we make the large sample case group’s DNA and the control group’s DNA with standardized principle. We statistically analyse the data,and then find out the positive snps(p<0.05, OR> 1.2).We want to find the functionable snps,susceptible snps and the cooperation effect within the genes.ResultsBy means of groupment of verification which are gotten by large samples,we choose 7 snps which are related to schizophrenia strongly, that is rs12991836 (ZEB2), rs1261117 (TCF4),rs7172342 (RORA), rs893290 (RORA) and rs7045881 (PLAA),rs1006737 (CACNA1C),rs10503256 (CSMD1)ConclusionsBy means of groupment of verification which are gotten by large samples.ZEB2, TCF4, RORA, PLAA, CACNA1C and CSMD1 maybe the susceptibility genes for schizophrenia.